Dried biological fluid spot analysis such as dried blood spot (DBS) analysis is becoming increasingly popular for pharmaceutical companies in clinical trials. Collection sites for clinical trials may sample blood spots (or other types of biological fluid spots) in the field, allow the spots to dry, and then ship the spots at a lower cost than liquid samples due to the non-biohazard status of dried blood spots and the less rigorous requirements for temperature control. Blood spotting is also becoming useful in preclinical work as analytical chemists are required to store samples for Incurred Sample Reanalysis (ISR) studies, and dried blood spots have proven to be an effective way to stabilize the analytes and the matrix. Typically, DBS samples are prepared by applying drops of blood, typically obtained from venipuncture of a human or animal, to an absorbent substrate (e.g., filter paper) of an appropriate composition. The blood saturates the substrate and is air dried for a period of time (e.g., several hours) sufficient to form an array of circular dried blood spots on the substrate. The spot-containing substrate may then be stored in a plastic container and transported as needed without needing to be frozen. The dried blood spots may thereafter be separated from the bulk substrate by punching the dried blood spots to create individual dried blood spot disks. Analytes such as pharmaceutical compounds, genetic materials, etc. (i.e., small molecules or high molecular weight molecules) may then be extracted from dried blood spots by any number of techniques and subjected to analytical testing. Other types of biological fluid samples may be dried and subsequently processed in an analogous manner.
The processing of dried blood spots and other types of biological fluid spots has many problems. For instance, labs typically utilize a single punching device for multiple sample spotting procedures. Even with the use of cleaning and sterilization procedures, the repeated use of the same punching device can cause carryover and cross-contamination. In addition, the conventional punch device is typically constructed of steel so as to be hard or strong enough to punch through conventional spotting substrates. The steel punching device often must be employed with a hammer to achieve effective punching Moreover, steel is generally not considered to be readily disposable as compared to other types of materials such as various plastics. Additionally, procedures such as extraction and collection of analytes and pass-through clean-up have conventionally required the use of instruments separate from the punch device. Typically protein precipitation or solid phase extraction is utilized to transfer the sample to a suitable matrix, remove interferences and concentrate or dilute the sample as necessary. Also, conventional processing of dried biological fluid spots has not been compatible with automated assaying systems.
In view of the foregoing, there is a need for providing apparatus or device configured for performing both punching and extraction/clean-up, and methods for punching and processing dried biological fluid spots utilizing a single apparatus or device capable of being implemented for both punching and processing. Additionally, there is a need for an apparatus or device that is readily disposable and thus readily replaceable after a single use.